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The improved compaction properties of mannitol after a moisture-induced polymorphic transition
Tomohiro Yoshinari1, Robert T Forbes, Peter York
1Postgraduate Studies on Pharmacology Technology, Drug Delivery Group, The School of Pharmacy, University of Bradford, BD7 1DP, Bradford, UK.
International Journal of Pharmaceutics
|May 20, 2003
Summary
Wet-granulation of mannitol induces a polymorphic transition and particle morphology change, creating delta-granules. These granules enhance tablet compaction properties, improving tensile strength and reducing capping in formulations with poorly compactable drugs.
Area of Science:
- Pharmaceutical Technology
- Materials Science
Background:
- Mannitol undergoes moisture-induced polymorphic transitions and morphology changes.
- Wet-granulation procedures can potentially induce in situ size-reduction and enhance compaction properties.
Purpose of the Study:
- To evaluate the compression properties of mannitol agglomerates formed during wet-granulation.
- To investigate the impact of these agglomerates on tablet formulation, particularly with poorly compactable drugs.
Main Methods:
- Powder X-ray diffraction and scanning electron microscopy to confirm polymorphic transition and morphology.
- Compression testing (Heckel analysis) to evaluate mechanical properties.
- Tablet formulation studies using phenylpropanolamine hydrochloride (PPA) as a model drug.
Main Results:
- Wet-granulation resulted in a polymorphic transition (delta to beta form) and formation of filament-like delta-granules.
- Tablets compressed with delta-granules showed 1.5 times higher tensile strength compared to other mannitol samples.
- Delta-granules exhibited enhanced plastic deformability, leading to improved compaction without fragmentation.
- Formulations with PPA using delta-granules produced excellent tablets without capping, unlike those with conventional mannitol.
Conclusions:
- The unique particle structure of delta-granules, characterized by primary particle size and surface area, significantly improves mannitol's compaction behavior.
- Delta-granules serve as effective excipients for preparing robust tablets, even with challenging model drugs like PPA.
- The improved compaction is attributed to particle characteristics rather than the polymorphic transition itself.